Sustained chronic tachyarrhythmias often cause a deterioration of
cardiac function known as tachycardia-induced cardiomyopathy or
tachycardiomyopathy.1 It has been
recognized that the tachycardiomyopathy occurs in experimental models2 and also in patients with supraventricular or
ventricular tachycarrhythmias.3-6
Generally, cardiac function
will recover if drug or catheter ablation therapy is successfully
performed. Phillips and Levine7 initially
presented this concept in 1949 for the relationship between
rapid atrial fibrillation and reversible left ventricular (LV) failure.
However, it might be difficult to define its cause and effect
relationship
when cardiomyopathy and tachycardia are identified simultaneously. The
reversibility of LV dysfunction may often be variable and the precise
mechanisms
of the pathophysiological features of this phenomenon should be
elucidated.
Although excellent and comprehensive review articles by Fenelon G, et
al.8 and Shinbane JS et al 9 regarding these topics have already been
published, I will firstly present a typical case and then review the
basic and clinical characteristics
of tachycardiomyopathy in this article.

A
13-year-old girl was admitted with a chief complaint of orthopnea. She
had been born with the congenital anomalies of spina bifida and common
cloacae. At birth, an artificial anal and urinal plasties had been
performed. At the age of 11 her urinary and anal tracts had been
surgically separated. After the operation she has been doing well, but
at the age of 13, orthopnea and edema of the lower extremities was
noticed. She was referred to pediatrics and diagnosed as having
congestive heart failure with atrial tachycardia. Digitalis, verapamil,
and a small dose of metoprolol were not effective in controlling her
arrhythmia, so she was referred to our department for further
evaluation and treatment.
Physical examination indicated a small build (body height 112cm, weight
26kg) with underdevelopment of the lower extremities. Chest X-ray
revealed marked cardiomegaly with a cardio-thoracic ratio of 77 % (Fig. 1A). On echocardiography, the left
ventricular ejection fraction (LVEF) and the diastolic dimension were
0.21 and 51 mm, respectively. Her ECG showed atrial tachycardia with a
heart rate of 150 beats per minute (bpm) and an upright P wave
configuration in the limb
leads of II,III, and aVf (Fig. 1B).
At
first we sought to perform an electrophysiological study, but the
venous approach for catheterization was quite difficult since the
development of her bilateral femoral vein had been hindered by the
operation for her congenital genito-urinal abnormality. Furthermore,
the patient and her family were reluctant to accept invasive
examination or treatment. Thereafter, we decided to prescribe
pilsicainide at an initial dose of 25 mg, and within 2 hours her
ectopic atrial tachycardia was converted to a sinus rhythm. It was
maintained by a daily dose of 75 mg pilsicainide from that day onward.
After 3 months, chest X-rays showed an improvement of the
cardiothoracic ratio to 46% (Fig. 1C), while
her sinus rhythm was maintained using the same prescription (Fig. 1D). On echocardiography, the LV EF improved
to 0.62 and the diastolic dimension decreased to 37 mm. She has been
well in the four years since, and repeated Holter recordings have
indicated the successful maintenance of sinus rhythm.

Coined by Gallagher JJ11 , the term
tachycardia-induced cardiomyopathy or tachycardiomyopathy refers to
impairment in LV function secondary to chronic tachycardia, which is
partially or completely reversible after normalization of heart rate
and/or rhythm irregularity. Later, Brugada P and Andries E12 defined that a "tachycardiomyopathy" is an
abnormality of systolic or diastolic function of the heart, or
both, usually resulting in heart dilatation and ultimately in heart
failure
caused by a high and/or irregular ventricular rate. This high and/or
irregular ventricular rate may result from any type of cardiac
arrhythmia.
Fenelon et al8 further classified
tachycardiomyopathy into two categories. They are "pure type" and
"impure type" tachycardiomyopathy. In the former, chronic tachycardia
causes LV dysfunction in a normal heart and completely recovers after
termination of the tachycardia. In the
latter, such a condition occurs in patients with structural heart
diseases,
and the cardiac dysfunction may only recover incompletely after
termination of the tachycardia. The incomplete recovery of LV function
might be the
result of long-term tachycardia inducing irreversible myocardial
injury.

Mechanism of Tachycardiomyopathy

There is no definite answer to the precise mechanism of
tachycardiomyopathy in the clinical setting.8,9 Several experimental studies have however been
helpful in understanding the pathophysiology of tachycardiomyopathy.

Basic mechanisms
Tomita et al13 investigated three groups
of pigs:1)rapid left atrial pacing for 3 weeks, 2)with a 4-week
recovery
period, and a 3)sham-group. In their experimental models, a continuous
pacing rate of more than 240 beats/min for 3 weeks provoked the
decrease
of cardiac output, dilatation of the left ventricle, reduced systolic
function
and diastolic dysfunction, such as increased LV end-diastolic pressure,
as well as neurohumoral abnormalities similar to human dilated
cardiomyopathy.
They found that LV wall thickness was reduced, but the
ventricular
mass itself did not change. After termination of the pacing, systolic
function recovered ,but diastolic function remained abnormal. Thus, the
severity of LV dysfunction was related to the duration of
tachyarrhythmias.
In
chronic-paced animal models, the response to beta-adrenergic
stimulation is known to be blunted. This may also be related to a
decrease in the density of the beta-adrenergic receptors.14,15 These facts are often
confirmed in clinical situations. Catecholamine concentrations in
patients with heart failure are increased at rest and during low-level
exercises, and attenuated during high-level exercises.16
Such inappropriate adrenergic responses may facilitate the development
of tachycardiomyopathy and therefore, the efficacy of adequate
beta-blocker therapy may be expected in treating tachycardiomyopathy.17 Actually, beta-blockers had favorable effects
in patients with dilated cardiomyopathy.18,19 Other neurohumoral activation has also been
noted with a marked elevation of plasma natriuretic peptides, rennin
activity and aldosterone levels.20
Regarding other cellular functions, chronic SVT induced cardiomyopathy
in swine was associated with decreased Na-K ATPase activity and
glycoside receptor density and affinity.21,22 Spinale et al reported that the contractile
function in isolated myocytes is decreased due to the blunted response
to any extracellular calcium overloads.23
According
to He JQ et al24, cellular remodeling in
heart failure results in the decreased density of T-tubules and L-type
Ca2+ channels, which contribute to abnormal EC coupling. It may
contribute
to the reduction of contractility in tachycardia-induced
cardiomyopathy.
Furthermore, Williams R et al25 referred
to
a relationship between myocardial protein gene expression and decreased
LV contractility in their canine model.
A
recent experimental study indicated that antioxidant vitamins such as
beta-carotene, ascorbic acid and alpha-tocopherol reduced tissue
oxidative stress in congestive heart failure and attenuated the
associated cardiac dysfunction in a rabbit model. In addition, they
also attenuated beta-receptor down regulation and sympathetic nerve
terminal abnormalities. Therefore, it was emphasized that antioxidant
therapy may be an efficacious method in treating human congestive heart
failure.26
In a
pig model of tachycardiomyopathy, Spinale et al27
observed a reduced myocardial blood flow reserve,
particularly in the subendocardium and a decrease in
endocardial/epicardial
flow ratio. No significant morphological changes in the coronary
vasculature
were observed. This suggests that the vascular structural changes were
not responsible for the abnormalities in myocardial blood flow. The LV
dysfunction and myocyte injury linked to tachycardiomyopathy are
thought
to be associated with reduced myocardial blood flow. Early recovery
from
supraventricular tachycardiomyopathy resulted in hypertrophy with
normal myocardial blood flow at rest, but significantly reduced
coronary reserve. However, these blood flow abnormalities in
tachycardiomyopathy have not sufficiently been evaluated in clinical
series.
In
relation to the basic mechanisms of myocardial cell hypertrophy, Clemo
et al28 tested the hypothesis that
cellular hypertrophy in congestive heart failure modulates
mechanosensitive channels. In canine models, swelling-activated inward
rectifying cation current (I circ, swell) is persistently activated in
tachycardiomyopathy. It is likely to be activated in multiple forms of
cardiac hypertrophy and failure and may contribute to dysrythmias and
altered contractile function. They suggested that I circ, swell may
represent a novel target for therapeutic interventions.
A
detailed summary of the functional and neurohumoral spectra of
experimental tachycardiomyopathy is described by Fenelon et al.8 in their review.
In
addition, recent studies elucidated that the progression of
tachycardiomyopathy to heart failure facilitates ionic channel
remodeling and it may contribute the generation of ventricular
tachyarrhythmias. There have been many studies related to the ionic
remodeling (K+ and Ca2+) of ventricular myocytes
in experimental animals by rapid-pacing induced heart failure.29,30A
reduction in
the density of transient potassium outward current(Ito) is the most
consistent ionic current change in cardiac failure. The density of Ito
is known to be variable regionally and transmurally, and it was reduced
differentially in heart failure.31Tomaselli GF et al32indicated that the down-regulation of Ito may generate
repolarization abnormalities and cause increased electrical instability
of the failing heart. A recent study also pointed out the
down-regulation of two components of the delayed rectifier potassium
current (Ikr and Iks) in the pacing-induced heart failure rabbit model.33It may prolong
the action potential at physiological cycle lengths and therefore
contribute to arrhythmogenesis in heart failure. Han W, et
al34studied
ionic
remodeling of cardiac purkinje cells(PCs) isolated from control and
pacing-induced heart failure dogs. Their results showed that remodeling
of K+ and Ca2+
currents occurs in PCs of tachycardia-induced heart failure dogs. Ik1
and
Ito density were significantly smaller in congestive heart failure PCS
and
cause a reduction of the repolarization reserve. They concluded that
the
results may explain the ventricular arrhythmogenesis, particulary
related
to triggered activity in PCs, in patients with heart failure.

Clinical mechanisms
In
clinical situations, tachycardiomyopathy is induced by various
supraventricular and ventricular arrhythmias. Particularly in
childhood, ectopic atrial tachycardia (EAT), a permanent form of
junctional reciprocating tachycardia (PJRT) are most prevalently
observed, which they are often incessant and refractory to
antiarrhythmic drugs, and this commonly results in tachycardiomyopathy.35
Human tachycardiomyopathy is considered to be similar to the mechanisms
of most experimental models. A small number of studies suggest a
hemodynamical changes in patients with tachycardiomyopathy.36 They are reduced LVEF, increased end-diastolic
and end-systolic volumes, and increased end-diastolic and pulmonary
artery pressures. Termination of the tachycardia lead to an improvement
of clinical symptoms, an increase of EF and a marked decrease of
end-systolic volumes. Concentric LV hypertrophy following recovery from
tachycardiomyopathy was not noted. Usually, the degree of LV
dysfunction is not always related to the tachycardia duration or rate.1 Thease reasons are why the determination of the
onset is quite difficult, since the patients without underlying
diseases are asymptomatic until congestive heart failure occurs. On the
other hand, patients with underlying heart disease are more likely to
progress toward heart failure.
Paelinck B et al37 reported an evaluation
method of myocardial contractile reserve in dilated cardiomyopathy with
atrial fibrillation by using low-dose dobutamine echocardiography. They
investigated using a wall motion score index, which was obtained by a
summation
of the individual wall motion scores of 16 segments of the left
ventricle
at baseline and after infusion of low-dose dobutamine as well as before
and after cardioversion . The patients who showed a marked increase of
LVEF at low-dose dobutamine and normalized EF at the follow-up were
considered
to have cardiomyopathy. These patient's wall motion score index had
significantly
improved, both at low-dose dobutamine and at the follow-up. On the
contrary,
no or low responders to dobutamine and wall motion score index were
diagnosed
as having dilated cardiomyopathy. It was suggested that low-dose
dobutamine echocardiography predicts the improvement in LVEF after
restoration of the sinus rhythm and is thus available in the
identification of tachycardiomyopathy.
Other factors related to LV function; age, underlying heart disease,
drugs, irregurality of ventricular rhythm, short atrioventricular
interval of less than 100ms are emphasized, yet remain to be determined.8
Regarding the mechanism of functional mitral regurgitation in
tachycardiomyopathy, Timek TA et al38
studied the valvular and ventricular 3D geometric perturbations
associated with MR in an ovine model
of tachycardia-induced cardiomyopathy. According to the findings, the
result of mitral annular dilatation and separation of the leaflet hinge
points are the primary cause, which then led to incomplete leaflet
coaptation and valve incompetence. Altered subvalvular leaflet
tethering did not appear to play a major role in the pathogenesis of
MR.

Clinical Diagnosis

A
definite diagnosis of tachycardiomyopathy is sometimes difficult. A
correct diagnosis can only be made by a normalization or improvement of
the impairment of LV function after control of the tachyarrhythmias.
However, it is also a fact that tachyarrhythmia control does not always
bring about the improvement of LV function in patients with
tachycardiomyopathy, and may simply reflect the irreversible stage of
tachycardiomyopathy and complicate the diagnosis. Thus, no specific
methods are available to identify the presence of tachycardiomyopathy
at present. Therefore, it is important to suspect the existence of this
condition from its history and clinical findings.
Fenelon et al8 proposed the following
criteria for the diagnosis of tachycardiomyopathy; in patients
presenting with;
1) dilatation of the heart or heart failure, 2) Chronic or very
frequent
cardiac arrhythmias, including incessant supraventricular tachycardia,
atrial fibrillation or flutter and incessant ventricular tachycardia.
They further pointed out that if chronic tachycardia continued more
than
10-15% of the day, with an atrial rate of more than 150% of that
predicted
for age, tachycardiomyopathy ensues.

Treatment

The
basic concept for the treatment of tachycardiomyopathy is in controling
the heart rate. The appropriate heart rate is beneficial for patients
with tachycardia-induced heart failure. The usual approaches for
tachycardiomyopathy are by both pharmacological and non-pharmacological
treatments.
In
pharmacological therapy, drug choice depends on the underlying
arrhythmias. In supraventricular tachycardia, digitalis or a Ca2+
antagonist (verapamil) are the common drugs of choice. Hayano M, et al39 reported a successful treatment of ectopic
atrial tachycardiomyopathy by digitalis and verapamil. After gaining
control of the heart rate, the
LV diastolic dimension and cardiothoracic ratio were improved. They
emphasized that initial medical treatment is preferable in the absence
of a clinical emergency.
Usually, class I
anti-arrhythmic drugs have a negative inotropic effect and therefore,
the clinical use of these drugs for tachycardiomyopathy should be
carefully decided according to the patient's background. The case
presented here also had ectopic atrial tachycardiamyopathy, which
was successfully treated with pilsicainide. This drug is a class Ic
drug with a strong sodium channel blocking action and has a relatively
short half-life compared to other Ic agents. In addition, a single oral
dose is often effective for terminating supraventricular arrhythmias.
For these reasons we cautiously administrated a single oral dose of
pilsicainide (25mg), and it eventually terminated the EAT. Sinus rhythm
was maintained at a dose of 75 mg/day and dramatic improvement of
cardiac function was observed. Thus, if for some reason, catheter
ablation cannot be performed as the first-line of therapy, class Ic
drugs, including pilsicainide are an available option for the treatment
of EAT-induced cardiomyopathy, provided that the patient is carefully
observed.
In pediatric cases, EAT or
PJRT is often incessant and commonly results in
tachycardiomyopathy. Amiodarone is the only available drug for
patients with impaired LV function and tachyarrhythmias.40 In pediatric
cases, EAT or PJRT is often incessant and commonly results in
tachycardiomyopathy. Chen R.P-C.41
reported a case of PJRT which was successfully treated
with amiodarone during the neonatal period. After 6 weeks systolic
function
improved. Complete resolution of ventricular tachycardia-induced
cardiomyopathy
by oral amiodarone in a young boy has also been reported.42 Treatment with other class III drugs including
dofetilide,
sotalol, ibutilide or azimilide may be another option. These class III
drugs prolong the action potential duration and may enhance the inward
calcium reflux resulting in increased contractility and are a favorable
choice for tachycardiomyopathy if adverse effects are avoided. However,
medical treatment is not always effective and safe, besides, several
available drugs are ineffective in such cases. Therefore, a
non-pharmacological approach is the next choice in the treatment.

Non-pharmacological approach

Catheter ablation
Since the introduction of radiofrequency (RF) ablation, the treatment
of tachyarrhythmias has been safely performed and favorable results
have
been obtained. Simultaneously, it has been proven that the cure or
control
of tachyarrhythmia could improve LV function and heart failure in
patitents with tachycardiomyopathy. Targeted arrhythmias are wide
ranging, including EAT43, PSVT or PJRT 44-47 atrial
fibrillation/flutter3,48
frequent isolated premature ventricular
extrasystole49, and ventricular
tachycardia 50-53. In
most of these
reports, cardiac function improved or normalized after successful RF
ablation. These facts lead us to believe that catheter ablation in
patients with tachycardiomyopathy should be performed as the first-line
therapy as soon as possible.
RF
ablation can even be used successfully even in a cardiac transplant
patient with atial tachycardia-induced cardiomyopathy.54

Surgical therapy
Similary, a surgical treatment is also effective for patients who
received operations to cure the tachyarrhythmias. Giorgi LV et al 55 reported the surgical treatment of an 11
year-old-girl with focal atrial tachycardia and congestive heart
failure which resulted in the improvement of LV function. Cruz FES et al4 reported the experience of surgical treatment of
PSVT induced cardiomyopathy in 8 of 17 patients. After an average
follow-up of 21.6 months, EF increased from 36% to 59%, LVDd decreased
from 56 mm to 49 mm. They acknowledged
the significance of surgery in such patients. Rabbani et al56 reported a case of DCM with EAT which was
treated surgiclly. The patient received surgical cryoablation and LV
function
was improved 1 month after the operation. If catheter ablation cannot
be performed as the first-line therapy for some reason, surgical
therapy
is an available option for the treatment of tachycardiomyopathy.

Prognosis

Generally, if tachyarrhythmias are properly treated, cardiac function
will recover. In bacic study, the recovery of LV systolic function
requires about 2 weeks from the termination of pacing. However, in
clinical situations, this may be quite variable both spatially and
temporally because the
length of tachycardia and underlying heart diseases are different in
each patient.

Conclusion

The
diagnosis of tachycardia-induced cardiomyopathy is not always simple,
but we should start therapy if the patient suffers from congestive
heart failure with tachyarrhythmias. This is because LV dysfunction may
be
recover after adequate treatment and it is the only way to make a
definite
diagnosis of tachycardiomyopathy.